Utilisation, expenditure and cost-effectiveness of cystic fibrosis drugs in Ireland: a retrospective analysis of a national pharmacy claims database.

BMJ Open. 2020 Nov 14;10(11):e040806

Authors: Smith A, Barry M

Abstract
OBJECTIVES: To determine the use and expenditure associated with cystic fibrosis (CF) modulator therapies in Ireland since their reimbursement in 2013.
DESIGN: A retrospective analysis of a national drug claims database.
SETTING: The data included in this study are nationally representative (Ireland).
PARTICIPANTS: Data on all persons receiving CF modulator therapies were included.
METHODS: We obtained national claims data for CF therapies from the Health Service Executive's Primary Care Reimbursement Service. We determined the use and expenditure associated with CF therapies from January 2012 to March 2020.
RESULTS: The increased prescribing of CF modulator therapies was associated with an approximate fivefold increase in expenditure from €23 million in 2013 to €113 million in 2019. Many patients who initiated lumacaftor/ivacaftor in 2017 went on to receive symptomatic therapies, and subsequently initiated tezacaftor/ivacaftor in 2019.
CONCLUSION: Despite none of these modulator therapies demonstrating value for money when subjected to health technology assessment, the associated Irish expenditure reached €113 million in 2019 alone.

PMID: 33191267 [PubMed - in process]

Evaluation of Pyocyanin induced systemic pathogenicity of Pseudomonas aeruginosa.

Pak J Pharm Sci. 2020 May;33(3):915-922

Authors: Rashid MI, Andleeb S, Ali A

Abstract
Pseudomonas aeruginosa (PA) is one of the most clinically significant nosocomial infectious agents. Clinical significance of this bacterium is intensified due to the phenomenon of its natural tendency for acquiring drug resistance mechanisms. PA produces pyocyanin (PCN), an important redox-active virulence factor. PCN has been detected in higher quantities in sputum samples of PA infected Cystic Fibrosis patients. PCN producing PA strains were isolated and characterized. Genomic 16s rRNA gene segment was amplified and sequenced (GenBank accession # jx280426). PCN was extracted and purified. In silico analysis yielded permeability and cytotoxic potential of PCN in modeled cell lines. PCN has high intestinal absorption, plasma protein binding potential, and permeability across biological membranes. Oral toxicity study in in silico rodent model classified PCN in class IV 'harmful if swallowed' (ld50 0.3-2g/kg). Cytotoxicity was assessed by oxidative stress levels in different organs in balb/c mice induced by intra peritoneal PCN injection. Significant alterations in oxidative stress levels in different organs of balb/c mice were observed. Increased levels of oxidative stress were observed in lungs, and heart, lower in liver and spleen while muscle tissues showed no significant difference in comparison to control.

PMID: 33191213 [PubMed - in process]

Electronic health nudges to improve reproductive health care for women with cystic fibrosis.

J Cyst Fibros. 2020 Nov 12;:

Authors: Roe AH, Yapalater S, Hadjiliadis D

PMID: 33191130 [PubMed - as supplied by publisher]

Outcomes and endpoints reported in studies of pulmonary exacerbations in people with cystic fibrosis: A systematic review.

J Cyst Fibros. 2020 Nov 12;:

Authors: McLeod C, Wood J, Schultz A, Norman R, Smith S, Blyth CC, Webb S, Smyth AR, Snelling TL

Abstract
BACKGROUND: There is no consensus about which outcomes should be evaluated in studies of pulmonary exacerbations in people with cystic fibrosis (CF). Outcomes used for evaluation should be meaningful; that is, they should capture how people feel, function or survive and be acknowledged as important to people with CF, or should be reliable surrogates of those outcomes. We aimed to summarise the outcomes and corresponding endpoints which have been reported in studies of pulmonary exacerbations, and to identify those which are most likely to be meaningful.
METHODS: A PROSPERO registered systematic review (CRD42020151785) was conducted in Medline, Embase and Cochrane from inception until July 2020. Registered trials were also included.
RESULTS: 144 studies met the inclusion criteria. A wide range of outcomes and corresponding endpoints were reported. Death, QoL and many patient-reported outcomes are likely to be meaningful as they directly capture how people feel, function or survive. Forced expiratory volume in 1-second [FEV1] is a validated surrogate of risk of death and reduced QoL. The extent of structural lung disease has also been correlated with lung function, pulmonary exacerbations and risk of death. Since no evidence of a correlation between airway microbiology or biomarkers with clinically meaningful outcomes was found, the value of these as surrogates was unclear.
CONCLUSIONS: Death, QoL, patient-reported outcomes, FEV1, and structural lung changes were identified as outcomes that are most likely to be meaningful. Development of a core outcome set in collaboration with stakeholders including people with CF is recommended.

PMID: 33191129 [PubMed - as supplied by publisher]

How to determine the mechanism of action of CFTR modulator compounds: A gateway to theranostics.

Eur J Med Chem. 2020 Nov 05;:112989

Authors: Amaral MD

Abstract
The greatest challenge of 21st century biology is to fully understand mechanisms of disease to drive new approaches and medical innovation. Parallel to this is the huge biomedical endeavour of treating people through personalized medicine. Until now all CFTR modulator drugs that have entered clinical trials have been genotype-dependent. An emerging alternative is personalized/precision medicine in CF, i.e., to determine whether rare CFTR mutations respond to existing (or novel) CFTR modulator drugs by pre-assessing them directly on patient's tissues ex vivo, an approach also now termed theranostics. To administer the right drug to the right person it is essential to understand how drugs work, i.e., to know their mechanism of action (MoA), so as to predict their applicability, not just in certain mutations but also possibly in other diseases that share the same defect/defective pathway. Moreover, an understanding the MoA of a drug before it is tested in clinical trials is the logical path to drug discovery and can increase its chance for success and hence also approval. In conclusion, the most powerful approach to determine the MoA of a compound is to understand the underlying biology. Novel large datasets of intervenients in most biological processes, namely those emerging from the post-genomic era tools, are available and should be used to help in this task.

PMID: 33190956 [PubMed - as supplied by publisher]

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Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers.

Am J Respir Crit Care Med. 2020 Nov 12;:

Authors: Dunican EM, Elicker BM, Henry T, Gierada DS, Schiebler ML, Anderson W, Barjaktarevic I, Barr RG, Bleecker ER, Boucher RC, Bowler RP, Christenson SA, Comellas A, Cooper CB, Couper D, Criner GJ, Dransfield M, Doerschuk CM, Drummond MB, Hansel NN, Han MK, Hastie AT, Hoffman EA, Krishnan JA, Lazarus SC, Martinez FJ, McCulloch CE, O'Neal WK, Ortega VE, Paine R, Peters S, Schroeder JD, Woodruff PG, Fahy JV

Abstract
BACKGROUND: The relative roles of mucus plugs and emphysema in mechanisms of airflow limitation and hypoxemia in smokers with chronic obstructive pulmonary disease (COPD) are uncertain.
METHODS: We analyzed computed tomography (CT) lung images and lung function in participants in the Subpopulations and Intermediate Outcome Measures in COPD Study. Radiologists scored mucus plugs on CT lung images and imaging software automatically quantified percent emphysema. Unadjusted and adjusted relationships between mucus plug score, percent emphysema, and lung function were determined using regression.
RESULTS: Among 400 smokers, 229 (57%) had mucus plugs and 207 (52%) had emphysema and subgroups could be identified with mucus dominant and emphysema dominant disease. Only 33% of smokers with high mucus plug scores had mucus symptoms. Mucus plug score and percent emphysema were independently associated with lower values for forced expiratory volume in one second and peripheral oxygen saturation (p values < 0.001). The relationships between mucus plug score and lung function outcomes were strongest in smokers with limited emphysema (p values <0.001). Compared to smokers with low mucus plug scores, those with high scores had worse COPD Assessment Test scores (17.4 ± 7.7 vs. 14.4 ± 13.3), more frequent annual exacerbations (0.75 ± 1.1 vs. 0.43 ± 0.85), and shorter 6-minute walk distance (329 ± 115 vs. 392 ± 117 meters)(p values < 0.001).
CONCLUSION: Symptomatically silent mucus plugs are highly prevalent in smokers and independently associate with lung function outcomes. These data provide rationale for targeting mucus-high/emphysema-low COPD patients in clinical trials of muco-active treatments.

PMID: 33180550 [PubMed - as supplied by publisher]

Linaclotide, lubiprostone and tenapanor improve gut fluidity and alkalinity in CFTR-deficient and F508del mutant mice via NHE3 inhibition.

Br J Pharmacol. 2020 Nov 11;:

Authors: Tan Q, di Stefano G, Tan X, Renjie X, Römermann D, Talbot SR, Seidler UE

Abstract
BACKGROUND: Constipation and intestinal obstructive episodes are major health problems in cystic fibrosis patients.
AIM: Three FDA-approved drugs against constipation-prone irritable bowel syndrome were tested for their ability to increase luminal fluidity and alkalinity in CFTR null (cftr-/- ) and F508del mutant (F508delmut/mut ) murine intestine, and the underlying mechanism of action was explored.
METHODS: Guanylate cyclase C agonist linaclotide, prostaglandin E1 analogue lubiprostone, and intestine-specific NHE3 inhibitor tenapanor were perfused through a ~3 cm jejunal, proximal or mid-distal colonic segment in anesthetized cftr-/- , F508delmut/mut , and WT mice. Net fluid balance was determined gravimetrically and alkaline output by pH-stat back titration.
RESULTS: Basal jejunal fluid absorptive rates were significantly higher, and basal HCO3 - output was significantly lower in cftr-/- and F508delmut/mut compared to WT mice. In cftr-/- and F508delmut/mut mice, all three agents significantly inhibited the fluid absorptive rate and increased alkaline output in the jejunum, and tenapanor and lubiprostone, but not linaclotide, also did so in the colon. After tenapanor pre-incubation, linaclotide elicited a robust fluid secretory response in WT jejunum, while no further change in absorptive rates was observed in cftr-/- and F508delmut/mut jejunum, suggesting that the increase in gut fluidity and alkalinity by linaclotide in CF gut is mediated via NHE3 inhibition. Lubiprostone also inhibited fluid absorption in cftr-/- and F508delmut/mut jejunum via NHE3 inhibition, but had a residual NHE3-independent effect.
SUMMARY AND CONCLUSIONS: Linaclotide, lubiprostone and tenapanor reduced fluid absorption and increased alkaline output in the CF gut. Their application may ameliorate constipation and reduce obstructive episodes in CF patients.

PMID: 33179259 [PubMed - as supplied by publisher]

Insights for the Growth of Stenotrophomonas maltophilia in a Diabetic Patient with Long-Term Antibiotic Use: A Case Study.

J Am Podiatr Med Assoc. 2020 Sep 01;110(5):

Authors: Huchital MJ, Kim J, Mantzoukas A, Lucido JV

Abstract
BACKGROUND: Stenotrophomonas maltophilia is an uncommon gram-negative bacterium often found in individuals with long-standing broad-spectrum antibiotic use or catheter use; individuals undergoing hemodialysis; and individuals with prolonged respiratory disease, specifically, cystic fibrosis. To our knowledge, there are few reported cases of S maltophilia being the causative pathogen of infection in a diabetic foot wound.
METHODS: Following multiple surgical procedures and deep tissue cultures, S maltophilia was determined to be a secondary opportunistic colonizer of the wound, necessitating a change in antibiotic therapy.
RESULTS: The cultured pathogen was sensitive to ceftazidime, levofloxacin, and trimethoprim-sulfamethoxazole. The treatment team chose to use ceftazidime, as it also provided antibiotic coverage for the initial wound and blood cultures. Change in antibiotic therapy was initiated following multiple surgical procedures and angioplasty of the lower limb. The patient was discharged with a peripheral intravenous central catheter for outpatient antibiotic therapy.
CONCLUSIONS: Prolonged exposure to broad-spectrum antibiotics in individuals with multiple comorbidities including diabetes mellitus provides an advantageous environment for growth of uncommon multidrug-resistant organisms. Stenotrophomonas maltophilia may complicate the treatment of diabetic foot infections as an opportunistic pathogen. Understanding the implication of long-term broad-spectrum antibiotic treatment in the diabetic patient is important in managing postoperative complications and determining the correct course of treatment. The emergence of atypical pathogens in diabetic wounds must be managed appropriately.

PMID: 33179060 [PubMed - in process]

Risk factors and clinical course of children with cystic fibrosis colonized with Staphylococcus aureus.

Trans R Soc Trop Med Hyg. 2020 Nov 11;:

Authors: Ghimire JJ, Gulla KM, Jat KR, Sankar J, Lodha R, Kabra SK

Abstract
BACKGROUND: The literature is limited on staphylococcal infection in children with cystic fibrosis (CF) from tropical countries. We aimed to study the risk factors and clinical course of children with CF infected with Staphylococcus aureus.
METHODS: In this chart review we compared demographic, clinical and spirometry characteristics in CF children with S. aureus alone (group A), both S. aureus and Pseudomonas aeruginosa (group B) and P. aeruginosa alone (group C) colonization.
RESULTS: We included 79 cases (group A, 22; group B, 19; group C, 38). There was no difference in age of onset of symptoms, age of diagnosis, age of first isolation and spirometry parameters before colonization between the groups. The median duration of follow-up was shorter in group A. After colonization, children in group A and group B had significantly lower mean Shwachman and Kulczycki (SK) scores (44.7±5.4 and 40.8±5.8, respectively) compared with group C (49.9±6.8). Pulmonary exacerbations and hospitalizations were significantly greater in the combined group. After colonization, group A had a significant deterioration in SK score and forced vital capacity (FVC).
CONCLUSIONS: S. aureus colonization, especially in combination with P. aeruginosa, in children with CF was associated with worsening of FVC and clinical severity score and increased pulmonary exacerbations.

PMID: 33179055 [PubMed - as supplied by publisher]

Atypical Cystic Fibrosis: Diagnosis at the Age of 57 Years.

Cureus. 2020 Oct 09;12(10):e10863

Authors: Sagesse GJ, Yadava S, Mandava A

Abstract
Cystic fibrosis (CF) is an autosomal recessive, multi-organ disorder found predominantly among Caucasians. It classically presents in childhood with chronic productive cough, malabsorption causing steatorrhea, and failure to thrive. We present a 75-year-old female diagnosed with CF at the age of 57 years, which highlights the natural history and challenges in the diagnosis of atypical CF, including broadening physicians' respiratory differential diagnosis, limited patient symptoms, and late age of symptom onset.

PMID: 33178516 [PubMed]

P.F508del editing in cells from cystic fibrosis patients.

PLoS One. 2020;15(11):e0242094

Authors: Smirnikhina SA, Kondrateva EV, Adilgereeva EP, Anuchina AA, Zaynitdinova MI, Slesarenko YS, Ershova AS, Ustinov KD, Yasinovsky MI, Amelina EL, Voronina ES, Yakushina VD, Tabakov VY, Lavrov AV

Abstract
Development of genome editing methods created new opportunities for the development of etiology-based therapies of hereditary diseases. Here, we demonstrate that CRISPR/Cas9 can correct p.F508del mutation in the CFTR gene in the CFTE29o- cells and induced pluripotent stem cells (iPSCs) derived from patients with cystic fibrosis (CF). We used several combinations of Cas9, sgRNA and ssODN and measured editing efficiency in the endogenous CFTR gene and in the co-transfected plasmid containing the CFTR locus with the p.F508del mutation. The non-homologous end joining (NHEJ) frequency in the CFTR gene in the CFTE29o- cells varied from 1.25% to 2.54% of alleles. The best homology-directed repair (HDR) frequency in the endogenous CFTR locus was 1.42% of alleles. In iPSCs, the NHEJ frequency in the CFTR gene varied from 5.5% to 12.13% of alleles. The best HDR efficacy was 2.38% of alleles. Our results show that p.F508del mutation editing using CRISPR/Cas9 in CF patient-derived iPSCs is a relatively rare event and subsequent cell selection and cultivation should be carried out.

PMID: 33175893 [PubMed - as supplied by publisher]

Burkholderia gladioli infection in a pediatric patient with cystic fibrosis: the clinical challenges of an emergent pathogen.

Minerva Pediatr. 2020 Nov 11;:

Authors: Belli G, Giovannini M, Dolce D, Terlizzi V, Orioli T, Taccetti G

PMID: 33174713 [PubMed - as supplied by publisher]

Research advances in molecular mechanisms underlying the pathogenesis of cystic fibrosis: From technical improvement to clinical applications (Review).

Mol Med Rep. 2020 Oct 16;:

Authors: Wei T, Sui H, Su Y, Cheng W, Liu Y, He Z, Ji Q, Xu C

Abstract
Cystic fibrosis (CF) is a chronic disease causing severe impairment to the respiratory system and digestive tracts. Currently, CF is incurable. As an autosomal recessive disorder, the morbidity of CF is significantly higher among Caucasians of European descent, whereas it is less pervasive among African and Asian populations. The disease is caused by identical mutations (homozygosity) or different mutations (heterozygosity) of an autosomal recessive mutation at position 7q31.2‑q31.1 of chromosome 7. Diagnostic criteria and guidelines work concurrently with laboratory detection to facilitate precise CF detection. With technological advances, the understanding of CF pathogenesis has reached an unprecedented level, allowing for increasingly precise carrier screening, more effective early stage CF intervention and improved prognostic outcomes. These advances significantly increase the life quality and expectancy of patients with CF. Given the numerous improvements in the field of CF, the current review summarized the technical advances in the study of the molecular mechanisms underlying CF, as well as how these improvements facilitate the clinical outcomes of CF. Furthermore, challenges and obstacles to overcome are discussed.

PMID: 33173976 [PubMed - as supplied by publisher]

Targeted Nanotherapeutics for Respiratory Diseases: Cancer, Fibrosis, and Coronavirus.

Adv Ther (Weinh). 2020 Oct 13;:2000203

Authors: Majumder J, Minko T

Abstract
Systemic delivery of therapeutics for treatment of lung diseases has several limitations including poor organ distribution of delivered payload with relatively low accumulation of active substances in the lungs and severe adverse side effects. In contrast, nanocarrier based therapeutics provide a broad range of opportunities due to their ability to encapsulate substances with different aqueous solubility, transport distinct types of cargo, target therapeutics specifically to the deceased organ, cell, or cellular organelle limiting adverse side effects and increasing the efficacy of therapy. Moreover, many nanotherapeutics can be delivered by inhalation locally to the lungs avoiding systemic circulation. In addition, nanoscale based delivery systems can be multifunctional, simultaneously carrying out several tasks including diagnostics, treatment and suppression of cellular resistance to the treatment. Nanoscale delivery systems improve the clinical efficacy of conventional therapeutics allowing new approaches for the treatment of respiratory diseases which are difficult to treat or possess intrinsic or acquired resistance to treatment. The present review summarizes recent advances in the development of nanocarrier based therapeutics for local and targeted delivery of drugs, nucleic acids and imaging agents for diagnostics and treatment of various diseases such as cancer, cystic fibrosis, and coronavirus.

PMID: 33173809 [PubMed - as supplied by publisher]

Severe pulmonary alveolar proteinosis with respiratory failure treated by intrapulmonary percussive ventilation.

Respirol Case Rep. 2020 Dec;8(9):e00676

Authors: Tashiro T, Tomita Y, Inaba M, Hayashi K, Hirata N, Sakagami T

Abstract
Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by abnormal accumulation of surfactant in the alveoli. Whole lung lavage (WLL) is the standard treatment for severe autoimmune PAP (aPAP); however, it is highly invasive. Intrapulmonary percussive ventilation (IPV) is a non-invasive technique that delivers small bursts of high-flow respiratory gas into the lung and mobilizes secretions. As IPV is beneficial for chronic respiratory diseases such as cystic fibrosis and bronchiectasis to reduce sputum, it was hypothesized that IPV will ameliorate aPAP by mobilizing and removing accumulated surfactant and foamy macrophages. Here, we report the case of a 52-year-old female with severe aPAP and progressive respiratory failure. She received intermittent IPV therapy for six months and thereby showed improvement in assessments of chest computed tomography (CT), lung function, and oxygenation. We suggest that IPV should be used as an alternative therapy for patients with aPAP and respiratory failure.

PMID: 33173585 [PubMed]

Factors influencing the acquisition and eradication of early Pseudomonas aeruginosa infection in cystic fibrosis.

J Cyst Fibros. 2020 Nov 07;:

Authors: Jackson L, Waters V

Abstract
In recent years considerable improvements have been made in increasing the life expectancy of patients with cystic fibrosis. New highly effective modulator therapies targeting the underlying defect in the cystic fibrosis transmembrane conductance regulator protein are expected to enhance lifespan even further. However, chronic Pseudomonas aeruginosa pulmonary infections continue to threaten CF patient lung health and mortality rates. Early and aggressive antibiotic eradication therapies targeting P. aeruginosa are standard practice, but these eradication therapies fail in 10-40% of patients. The reasons for P. aeruginosa eradication failure remain unclear. Thus, this review summarizes the evidence to date for pseudomonal acquisition and eradication failure in the cystic fibrosis lung. A complex combination of host and bacterial factors are responsible for initial establishment of P. aeruginosa pulmonary infections. Moreover, host and pseudomonal factors, polymicrobial interactions, and antimicrobial limitations in relation to P. aeruginosa eradication therapy failure are summarized.

PMID: 33172756 [PubMed - as supplied by publisher]

JSRV Intragenic Enhancer Element Increases Expression from a Heterologous Promoter and Promotes High Level AAV-mediated Transgene Expression in the Lung and Liver of Mice.

Viruses. 2020 Nov 06;12(11):

Authors: Yu DL, Chow N, Wootton SK

Abstract
Jaagsiekte sheep retrovirus (JSRV) induces tumors in the distal airways of sheep and goats. A putative intragenic enhancer, termed JE, localized to the 3' end of the JSRV env gene, has been previously described. Herein we provide further evidence that the JE functions as a transcriptional enhancer, as it was able to enhance gene expression when placed in either forward or reverse orientation when combined with a heterologous chicken beta actin promoter. We then generated novel composite promoters designed to improve transgene expression from adeno-associated virus (AAV) gene therapy vectors. A hybrid promoter consisting of the shortest JE sequence examined (JE71), the U3 region of the JSRV long terminal repeat (LTR), and the chicken beta actin promoter, demonstrated robust expression in vitro and in vivo, when in the context of AAV vectors. AAV-mediated transgene expression in vivo from the hybrid promoter was marginally lower than that observed for AAV vectors encoding the strong CAG promoter, but greatly reduced in the heart, making this promoter/enhancer combination attractive for non-cardiac applications, particularly respiratory tract or liver directed therapies. Replacement of the murine leukemia virus intron present in the original vector construct with a modified SV40 intron reduced the promoter/enhancer/intron cassette size to 719 bp, leaving an additional ~4 kb of coding capacity when packaged within an AAV vector. Taken together, we have developed a novel, compact promoter that is capable of directing high level transgene expression from AAV vectors in both the liver and lung with diminished transgene expression in the heart.

PMID: 33172105 [PubMed - in process]

Bile Acid Signal Molecules Associate Temporally with Respiratory Inflammation and Microbiome Signatures in Clinically Stable Cystic Fibrosis Patients.

Microorganisms. 2020 Nov 06;8(11):

Authors: Flynn S, Reen FJ, Caparrós-Martín JA, Woods DF, Peplies J, Ranganathan SC, Stick SM, O'Gara F

Abstract
Cystic fibrosis (CF) is a congenital disorder resulting in a multisystemic impairment in ion homeostasis. The subsequent alteration of electrochemical gradients severely compromises the function of the airway epithelia. These functional changes are accompanied by recurrent cycles of inflammation-infection that progressively lead to pulmonary insufficiency. Recent developments have pointed to the existence of a gut-lung axis connection, which may modulate the progression of lung disease. Molecular signals governing the interplay between these two organs are therefore candidate molecules requiring further clinical evaluation as potential biomarkers. We demonstrate a temporal association between bile acid (BA) metabolites and inflammatory markers in bronchoalveolar lavage fluid (BALF) from clinically stable children with CF. By modelling the BALF-associated microbial communities, we demonstrate that profiles enriched in operational taxonomic units assigned to supraglottic taxa and opportunistic pathogens are closely associated with inflammatory biomarkers. Applying regression analyses, we also confirmed a linear link between BA concentration and pathogen abundance in BALF. Analysis of the time series data suggests that the continuous detection of BAs in BALF is linked to differential ecological succession trajectories of the lung microbiota. Our data provide further evidence supporting a role for BAs in the early pathogenesis and progression of CF lung disease.

PMID: 33172004 [PubMed]

Impaired Ratio of Unsaturated to Saturated Non-Esterified Fatty Acids in Saliva from Patients with Cystic Fibrosis.

Diagnostics (Basel). 2020 Nov 08;10(11):

Authors: Gelzo M, Iacotucci P, Carnovale V, Castaldo A, Comegna M, Cernera G, Corso G, Castaldo G

Abstract
Impaired salivary non-esterified fatty acids (NEFA) levels have been previously observed in cystic fibrosis (CF). This study aimed to characterize the salivary NEFA profile in CF and to examine whether the alterations are related to the pancreatic status and/or lung disease severity. We analyzed salivary NEFA, cholesterol and interleukin-6 (IL-6) in CF patients (n = 66) and healthy subjects (n = 48). CF patients showed higher salivary levels of cholesterol, total NEFA (that was negatively correlated with serum triglycerides), unsaturated NEFA/saturated NEFA (U/S NEFA) ratio and IL-6 than controls. The U/S NEFA ratio was positively correlated with IL-6 in both patients and controls, suggesting an association between this parameter and local inflammation independently from the disease. No correlation between salivary lipids and pancreatic status was observed, while the U/S NEFA ratio was higher in patients with severe lung disease than mild/moderate severity and may represent a prognostic marker of lung disease in CF.

PMID: 33171650 [PubMed]